Sprowls Samuel A, Saralkar Pushkar, Arsiwala Tasneem, Adkins Christopher E, Blethen Kathryn E, Pizzuti Vincenzo J, Shah Neal, Fladeland Ross, Lockman Paul R
Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA.
Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA.
Pharmaceutics. 2021 May 19;13(5):756. doi: 10.3390/pharmaceutics13050756.
The blood-brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, , is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of for new drug candidates using both intravenous and in situ protocols. Additionally, the single uptake method can be used to determine in heterogeneous pathophysiological conditions such as stroke, brain cancers, and Alzheimer's disease. In this review, we briefly cover the anatomy and physiology of the BBB, discuss the impact of efflux transporters on solute uptake, and provide an overview of the single-timepoint method for determination of values. Lastly, we compare preclinical experimental results with human parallels.
血脑屏障（BBB）限制溶质从脑微血管毛细血管系统腔向实质的移动。单向转运常数 是单个分子跨血脑屏障转运的速率。对于新药候选物，可使用静脉内和原位方案通过单次和多次摄取实验来测定 。此外，单次摄取方法可用于在中风、脑癌和阿尔茨海默病等异质性病理生理条件下测定 。在本综述中，我们简要介绍血脑屏障的解剖学和生理学，讨论外排转运体对溶质摄取的影响，并概述用于测定 值的单时间点方法。最后，我们将临床前 实验结果与人体相应结果进行比较。
